CMOP±R in the Treatment of Untreated Non-Hodgkin's Lymphoma

A Single-arm, Multi-center, Prospective Clinical Study of Mitoxantrone Hydrochloride Liposome Injection-based CMOP±R Regimen in the Treatment of Newly Diagnosed Non-Hodgkin's Lymphoma

This is a prospective, single arm, multicenter study to evaluate the safety and efficacy of CMOP±R in patients with newly diagnosed non-Hodgkin's lymphoma.

Study Overview

• Status: Not yet recruiting
• Conditions: NHL
• Intervention / Treatment: Drug: CMOP±R

Detailed Description

This is a single-arm, open label, multi-center clinical study to evaluate the safety and efficacy of mitoxantrone hydrochloride liposome in combination with Cyclophosphamide, Vincristine, Prednisone and/or Rituximab(CMOP±R) in patients with newly diagnosed non-Hodgkin's lymphoma. Mitoxantrone hydrochloride liposome will be given on day 1 at dose of 18 mg/m2 and be combined with cyclophosphamide, vincristine, prednisone and/or Rituximab. Each cycle consists of 28 days. A maximum of 8 cycles(6×CMOP±R+2×R) of therapy are planned.

• Study Type: Interventional
• Enrollment (Estimated): 197
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Haiwen Huang; Phone Number: 13962154846; Email: huanghaiwen@suda.edu.cn
• Study Contact Backup: Name: Haiwen Huang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients fully understand this study, voluntarily participate and sign the informed consent (ICF);
• Age: 18-75 years old;
• Expected survival time ≥ 3 months;
• Histopathologically diagnosed newly diagnosed non-Hodgkin's lymphoma;
• Must have at least one evaluable or measurable lesion that meets the Lugano 2014 criteria: lymph node lesions, measurable lymph nodes must have a long diameter >1.5cm; non-lymph node lesions, measurable extranodal lesions must have a long diameter >1.0cm;
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2.
• Bone marrow function: Absolute neutrophil count (ANC) ≥1.5×10^9/L, Platelet count (PLT) ≥75×10^9/L, Hemoglobin(HB)≥ 80 g/L(Restriction may be relaxed in patients with bone marrow involvement, Absolute neutrophil count (ANC) ≥1.0×10^9/L, Platelet count (PLT) ≥50×10^9/L, Hemoglobin(HB)≥ 75g/L);
• Liver and kidney function: serum creatinine ≤ 1.5 times the upper limit of normal value; AST and ALT ≤ 2.5 times the upper limit of normal value (for patients with liver invasion ≤ 5 times the upper limit of normal value); total bilirubin ≤ 1.5 times the upper limit of normal value (for patients with liver invasion ≤ 3 times the upper limit of normal value);

Exclusion Criteria:

• Subjects have previously received anthracyclic drug pretreatment;
• Hypersensitivity to any study drug or its components;
• Uncontrollable systemic diseases (such as advanced infection, uncontrollable hypertension, diabetes, etc.);
• Heart function and disease meet one of the following conditions: a) long QTc syndrome or QTc interval >480 ms; b) complete left bundle branch block, grade II or III atrioventricular block; c) Serious and uncontrolled arrhythmias requiring drug treatment; d) New York Heart Association grade ≥ III; e) Cardiac ejection fraction (LVEF) lower than 50%;f) A history of myocardial infarction, unstable angina pectoris, severe unstable ventricular arrhythmia or any other arrhythmia requiring treatment, a history of clinically serious pericardial disease, or ECG evidence of acute ischemia or active conduction system abnormalities within 6 months before recruitment.
• Active hepatitis B and C infection (positive hepatitis B virus surface antigen and more than 1x10^3 copies/mL of hepatitis B virus DNA; more than 1x10^3 copies/mL of hepatitis C virus RNA);
• Human immunodeficiency virus (HIV) infection (positive HIV antibody);
• Suffering from other malignant tumors in the past or at the same time (except for effectively controlled non-melanoma skin basal cell carcinoma, breast/cervix carcinoma in situ, and other malignant tumors that have been effectively controlled without treatment in the past five years);
• Suffering from primary or secondary central nervous system (CNS) lymphoma or a history of CNS lymphoma at the time of recruitment;
• Pregnant and lactating women and patients of childbearing age who are unwilling to take contraceptive measures;
• Other researchers judge not to Eligibility to participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CMOP±R; All enrolled patients. All patient who signed the consent form for participation to the study.

Drug: CMOP±R; Drug: Mitoxantrone hydrochloride liposome Mitoxantrone hydrochloride liposome (18 mg/m^2) on day 1, every 4 weeks; Drug: Cyclophosphamide Cyclophosphamide(750 mg/m^2) on day 1, every 4 weeks; Drug: Vincristine Vincristine (1.4mg/ m2，Max dose 2mg) will be administered on day 1(Or at the discretion of the investigator, use other vinblastine drugs with the same mechanism, such as vindesine 2-3 mg/m2 on day 1), every 4 weeks; Drug: Prednisone Prednisone (100 mg) will be taken orally from day 1-5(Or equivalent dose of dexamethasone at 15mg), every 4 weeks; Drug: Rituximab Rituximab (375mg/m^2) on day 0, every 4 weeks, only with CD20-positive lymphomas are evaluated by the investigator.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rate (CRR)	Response is assessed according to the 2014 lugano criteria.Percentage of participants with complete response was determined on 2014 Lugano criteria.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Response is assessed according to the 2014 lugano criteria.The total percentage of patients with complete response（CR ）and partial response（PR).	3 years
Progression-Free-Survival (PFS)	From the time subjects were enrolled to the time of disease progression (in any way) or death from any cause.Progression-free survival (PFS) was analyzed using Kaplan-Meier method, and 95% bilateral confidence intervals were calculated.	3 years
Duration of Response (DOR)	The time between meeting the criteria for treatment effectiveness (first recorded complete or partial response) and the first clear recurrence or progression.Duration of response (DoR) was analyzed using Kaplan-Meier method, and 95% bilateral confidence intervals were calculated.	3 years
Overall survival (OS)	From the date of inclusion to date of death, irrespective of cause.Overall survival (OS) was analyzed using Kaplan-Meier method, and 95% bilateral confidence intervals were calculated.	3 years
Progression of disease within 2 years(POD24)	The rate of patients with disease progression within 24 months of receiving first-line treatment at the start of enrollment.	3 years
Treatment-emergent adverse events (TEAEs)	The safety of the drug was evaluated by NCI-CTC AE 5.0 standard.Hematologic and non-hematologic toxicity.To identify the incidence of TEAEs with NCI-CTC AE 5.0 standard.	From the initiation of the first dose to 28 days after the last dose
Changes in cardiac safety indicators	The change value of LVEF% from baseline, and its mean, median, standard deviation, maximum and minimum values were statistically described.	3 years

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Investigators: Principal Investigator: Haiwen Huang, The First Affiliated Hospital of Soochow University, Suzhou, China

Study record dates

Study Major Dates

• Study Start (Estimated): July 10, 2024
• Primary Completion (Estimated): August 31, 2025
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: June 16, 2024
• First Submitted That Met QC Criteria: June 30, 2024
• First Posted (Actual): July 3, 2024

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: June 30, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Mitoxantrone hydrochloride liposome; newly diagnosed non-Hodgkin's lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: CSPC-DED-NHL-K03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No